Monday, May 02, 2016

EID Journal: Revisiting The Oseltamivir Effectiveness Debate

Credit Wikipedia

#11,332

Over the past 10 years we've been witness to both the repeated demonization and the resultant defense (by public health agencies) of the neuraminidase inhibitor (NAI) antiviral oseltamivir, better known as Tamiflu(c).

Fueling this media frenzy have been a number of Cochrane group analyses that foundinsufficient evidence that oseltamivir substantially reduces seasonal influenza complications in healthy adults.

And for mild to moderate seasonal influenza - in healthy adults - the advantages of taking the drug do appear to be modest at best. A reduction, on average, of less than a day of symptoms.

But in severe influenza, the benefits have been far more pronounced.

The problem is, while robust Randomized Controlled Trials (RCTs) exist for mild influenza, they do not (and ethically, cannot) be mounted for severe, life threatening flu. We are therefore left to draw our conclusions based on less rigorous, yet still compelling, observational data.

And most impressively . . .in Study: Antiviral Therapy For H5N1, out of 308 H5N1 cases studied, the overall survival rate was a dismal 43.5%. But . . . of those who received at least one dose of Tamiflu . . . 60% survived . . . as opposed to only 24% who received no antivirals.

Because of these (and other) studies, we’ve seen a push back by public health
agencies against the negative perceptions of antivirals, and advocacy for their early use in cases of severe flu:

All of which brings us to a new Perspective article published today in the EID Journal that reviews the both the existing RCT data along with an abundance of observational data, and offers some intriguing hints that oseltamivir might also modulate excess cytokine production (cytokine storm) in patients with severe flu infection.

The authors argue that the existing trials based on patients with relatively mild disease should not be used to drive policies on the treatment of severe influenza.

I've only posted the abstract from a much larger discussion, so follow the link to read the review in full.

Abstract

A debate about the market-leading influenza antiviral medication,
oseltamivir, which initially focused on treatment for generally mild
illness, has been expanded to question the wisdom of stockpiling for use
in future influenza pandemics.

Although randomized controlled trial
evidence confirms that oseltamivir will reduce symptom duration by 17–25
hours among otherwise healthy adolescents and adults with
community-managed disease, no randomized controlled trials have
examined the effectiveness of oseltamivir against more serious outcomes.

Observational studies, although criticized on methodologic grounds,
suggest that oseltamivir given early can reduce the risk for death by
half among persons hospitalized with confirmed infection caused by
influenza A(H1N1)pdm09 and influenza A(H5N1) viruses. However, available
randomized controlled trial data may not be able to capture the effect
of oseltamivir use among hospitalized patients with severe disease.

We
assert that data on outpatients with relatively mild disease should not
form the basis for policies on the management of more severe disease.